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Background: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy., Methods: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment)., Results: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48., Conclusions: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment., Competing Interests: Conflict of interest Armuzzi A.: Consultant: AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda. Lecture fees: AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Falk, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix Research grants: MSD, Takeda, Pfizer, Biogen Saibeni S.: Advisory board, lecture fees, consultancy for: AbbVie, Arena, Janssen, Ferring, Gilead, MSD, Takeda Scaldaferri F.: MSD, Jansen, Takeda, Sandoz, Ferring, Pfizer Geccherle A.: Served as a speaker, and/or advisory board member for the following organisations: AbbVie, Takeda, Janssen. Soriano A.: served as speaker and/or consultant and/or advisory board member and/or received fees from Janssen, Takeda, Pfizer, Novartis. Orlando A.: AO received lecture grants and/or served as an advisory board member for: AbbVie, Biogen, Chiesi, Janssen-Cilag MSD, Galapagos, Pfizer, Samsung Bioepis, Sofar, and Takeda Pharmaceuticals. Principi M.B.: Advisory boards, lectures fee, for Abbvie, Janssen, Pfizer, MDS,Takeda. Sarpi L.: MSD Cappello M: consultant for Takeda, Janssen-Cilag, Galapagos, Ferring, Biogen, speaker for Takeda, Biogen, Janssen-Cilag, Galapagos, Ferring D'Incà R.: Advisor for MSD, Takeda, Janssen, Biogen Lecture fees: Galapagos Bossa F.: Advisory board per Janssen; Pfizer; Celgene; Galapagos; Takeda Bezzio C.: received lecture fees and served as a consultant for Takeda, MSD, Ferring, Galapagos and Janssen., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis., Aims: to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription., Methods: This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD., Results: Seventy patients (64 Crohn's disease / 6 ulcerative colitis) were enrolled. The median follow-up on ustekinumab therapy was 10.7 months (range, 1.4-67.3). Twelve patients (17.1%) withdrew the treatment after a median of 7.4 months (range, 0.9-23.8). The cumulative probability of maintaining ustekinumab treatment was 97.1% at 6 months and 77.1% at 12 months. Among the 56 patients with baseline active IBD, 34 (60.7%) were in clinical remission at the last follow-up visit. Their cumulative probability of achieving clinical remission was 84.7% and 63.9% at 6 and 12 months, respectively. Two patients stopped ustekinumab for an adverse event., Conclusions: Subcutaneous ustekinumab had a good effectiveness profile for IBD patients treated for concomitant dermatological or rheumatological conditions., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: In several animal species the pancreas has the capacity to partially regenerate in a self regulating process. A complex network of growth factors modulates this process. There is evidence that bombesin stimulates pancreatic regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce the transcriptional upregulation of genes involved in cell proliferation. The aims of our study were to determine whether bombesin stimulates pancreatic growth in large mammals and whether this event requires Shc-MAP kinase pathway upregulation., Methods: Three groups of pigs were submitted to sham operation (group 1); to subtotal (70%) distal pancreatectomy (group 2), and to subtotal pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group 3). After a 4-week follow-up a second laparotomy was performed, and the residual pancreas removed. p46Shc, p52Shc and p66Shc, Grb2, and p42/p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts., Results: In vivo bombesin administration resulted in: 1) approximately 100% growth of pancreatic duodenal lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold increase in the rate of pancreatic acinar cell proliferation. Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time- and concentration-dependent stimulation of p46Shc/p52Shc phosphorylation, Shc-Grb2 complex formation, and p42/p44 MAP kinase activation. In vivo bombesin administration significantly upregulated p46Shc/p52Shc and MAP kinase expression and/or activity in whole pancreatic extracts., Conclusions: In vivo chronic bombesin administration stimulates pancreatic regeneration after pancreatectomy in large mammals. Bombesin-stimulated pancreatic growth is associated with upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.

Objectives: Laparoscopic cholecystectomy (LC) has become the treatment of choice for patients with symptomatic cholelithiasis. About 10% of patients with symptomatic gallstones may bear associated common bile duct (CBD) stones. The preferred approach to these patients is the removal of CBD stones by endoscopic retrograde cholangiography (ERCP) before LC. However, ERCP before LC should be performed only in patients with suspected choledocholithiasis. The aims of this study were to: 1) generate an efficacious predictive model for selecting patients with suspected choledocholithiasis to submit to preoperative ERCP, and 2) test the safety of the endoscopic/laparoscopic procedure., Methods: Historical, biochemical, and ultrasonographic data were collected prospectively. Receiver operating characteristics curve analysis was adopted for determining optimal biochemical and ultrasonographic cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones was also employed., Results: The optimal model predicted a 95% probability of CBD stones in a patient who presented with elevated ALP (over 300 IU/L) and ALT (over 40 IU/L) levels and CBD dilation > 8 mm at ultrasonography. Endoscopic removal of CBD stones was achieved in 95% of patients, with minimal morbidity and no mortality., Conclusions: The identified independent predictors of CBD stones are highly efficient selectors of patients with choledocholithiasis. Moreover, endoscopic removal of CBD stones before LC is a safe and efficacious procedure.

There is recent evidence that nitric oxide, a soluble gas produced from L-arginine, is released by the smooth muscle cells and neurons of the gastrointestinal tract where it exerts a myorelaxive action. However, little is known about the effects nitric oxide has on gastric and gallbladder motility during the inter- and postprandial phases in man. We therefore investigated the effects 200 mg/kg/hr L-arginine exerts on the gastric and gallbladder motility induced by 2 mg/kg erythromycin or a liquid meal in 21 subjects in a double-blind, placebo-controlled study. Gastric and gallbladder emptying were evaluated by sonography. Fasting antral motility was expressed as antral motility index (MI). In fasting subjects, L-arginine administration determined a threefold increase in plasma nitrite concentrations. Administration of erythromycin caused a significant rise in the antral MI, which was inhibited by L-arginine (P < 0.05). Ingestion of a liquid meal also significantly increased antral MI, but it returned to basal values 90 min after the end of the meal. Although L-arginine administration caused a significant reduction in the antral MI (P < 0.05), it did not inhibit gastric emptying. L-Arginine provoked an approximately 40% increase in basal gallbladder volume, completely blocked erythromycin-induced emptying, and partially, but significantly, prevented the emptying induced by a liquid meal (P < 0.01). Our study suggests that nitric oxide may be implicated in the physiological modulation of gastric and gallbladder motility during the inter- and postprandial phases in man.